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Halogenated benzimidazoles and benzotriazoles as inhibitors of the NTPase/helicase activities of hepatitis C and related viruses.
Kinetic studies indicated that, unlike the case with casein kinase 2, the mode of action of the inhibitors vs the helicases is not by interaction with the catalytic ATP-binding site, but rather by occupation of an allosteric nucleoside/nucleotide binding site. Expand
Purification and Characterization of West Nile Virus Nucleoside Triphosphatase (NTPase)/Helicase: Evidence for Dissociation of the NTPase and Helicase Activities of the Enzyme
Characterization of the NTPase activity of the WN virus enzyme revealed that optimum conditions with respect to the Mg2+requirement and the monovalent salt or polynucleotide response differed from those of other flavivirus NTPases. Expand
Inhibition of the helicase activity of HCV NTPase/helicase by 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide-5 '-triphosphate (ribavirin-TP).
The results suggest that derivatives of ribavirin-TP with enhanced stability towards hydrolytic attack may be effective inhibitors of the enzyme. Expand
Modified 5′‐Trityl Nucleosides as Inhibitors of Plasmodium falciparum dUTPase
Variations of the 5′‐trityl group, the introduction of various substituents at the 3′‐position of deoxyuridine, and modifications of the base result in loss of enzyme inhibition and significant decreases in antiplasmodial action. Expand
High-Yield Regioselective Thiation of Biologically Important Pyrimidinones, Dihydropyrimidinones and Their Ribo, 2′-Deoxyribo and 2′, 3′-Dideoxyribo Nucleosides
Abstract Convenient and high-yield regioselective thiation procedures based on the use of the Lawesson reagent in different solvents, are described for conversion of the 2- and 4-keto, and 2,Expand
2-Thio derivatives of dUrd and 5-fluoro-dUrd and their 5'-monophosphates: synthesis, interaction with tumor thymidylate synthase, and in vitro antitumor activity.
The beta-anomer 1 exhibited antitumor activity in a mouse leukemic cell line L5178Y (IC50 approximately 10(-6) M), hence 40-100-fold weaker than 5-fluoro-dUrd, but exhibited at least 10-fold higher selectivity with respect to the tumor cells than the beta-Anomer 1. Expand
Studies on the interaction with thymidylate synthase of analogues of 2'-deoxyuridine-5'-phosphate and 5-fluoro-2'-deoxyuridine-5'-phosphate with modified phosphate groups.
5-FdUMP and its analogues exhibited differing interactions with two binding sites on the enzyme molecule, consistent with cooperativity of binding, and a convenient procedure is described for the synthesis of 5-fluoro-2'-deoxyuridine-5'-methylphosphonate, applicable also to the preparation of other 5'-methyl phosphonate analogues. Expand
Interaction of 2-thio-5-fluoro-dUMP and 4-thio-5-fluoro-dUMP with mammalian normal and tumour and helminthic thymidylate synthases: influence of C(4)-substituents on specificity for enzyme
The results suggest that an interplay between substituents at C(4) and C(5) of the pyrimidine ring may affect the specificity of thymidylate synthase inactivation. Expand
Trichinella spiralis and Trichinella pseudospiralis: developmental patterns of enzymes involved in thymidylate biosynthesis and pyrimidine salvage
Comparisons of comparative studies on inhibition of purified T. spiralis and rat thymidylate synthases by substrate indicated only dUMP analogues to show feeble selectivity towards the parasite enzyme. Expand
Partial selective inhibition of HIV-1 reverse transcriptase and human DNA polymerases γ and β by thiated 3'-fluorothymidine analogue 5'-triphosphates.
The synthesis of 5'-triphosphates of thiated FLT analogues was undertaken and their interaction with recombinant HIV-1 RT and human DNA polymerases γ (pol γ) and β (pol β) was investigated, and results point to partially selective inhibition of HIV RT by thiated 3'-fluorothymidine 5'- triphosphate analogues. Expand